We are interested in the factors responsible for the exquisite bronchial sensitivity found in patients with bronchial asthma. This is a continuation of a genetic family study of host factors in bronchial asthma. This study deals with factors that may be involved in determining the natural history of bronchial asthma in the general population. One of the questions in this study is whether the bronchial sensitivity of asthmatic individuals to methacholine occurs at an early age even before clinical manifestation of the disease occurs. We intend to use the methacholine inhalation challenge test as the method of defining bronchial reactivity and possibly using this as a marker for eluicidation of its genetic characteristics. Another major part of this study is to determine whether asthma is acquired, genetically transmitted, and/or the result of interaction of environmental and host factors. We intend to study the natural history of asthma and methacholine sensitivity in patients who currently have asthma, former asthmatics, their atopic and non-atopic siblings, and concordant and discordant twin pairs. We will study the genetic characteristics of predisposition of asthma, in the above high risk groups as well as low risk groups such as non-atopic families. Parameters to be assessed include methacholine tolerance, allergy history and skin tests, serum IgE, protease inhibitor (Pi) types, and histocompatibility antigens. We will determine the sensitivity and specificity of ultrasonically nebulized distilled water (UNDW) as a test for bronchial asthma. We will compare the response of UNDW and cold air hyperventilation (CAHC) in subjects with asthma and to utilize these challenges to study the pathophysiology of asthma.